Biologic Characteristics of Interval and Screen-Detected Breast Cancers

BACKGROUND: Interval breast cancer is defined as a cancer that is detected within 12 months after a negative mammogram. The failure of mammography to detect breast cancer depends on testing procedures, radiologist interpretation, patient characteristics, and tumor properties. Although errors by radiologists explain some interval cancers, another explanation is that the tumor is rapidly growing and was too small to be detected on the last mammogram. To determine whether markers of tumor growth rate are associated with risk of an interval cancer, we conducted a population-based study with the use of data collected statewide by the New Mexico Mammography Project. METHODS: Among women who received a mammographic examination from 1991 throughout 1993, we ascertained records of all patients with breast cancer diagnosed within 12 months of a negative screening mammographic examination (interval cancers) and corresponding tumor samples, when available. We selected an age- and ethnicity-matched comparison group of control patients with screen-detected breast cancers diagnosed during the same period. In tumor samples, p53, bcl-2, and Ki-67 were examined immunologically and the apoptotic index was assessed histologically. We used logistic regression to determine whether interval cancers were associated with selected demographic, radiologic, and biologic characteristics. RESULTS: It is more likely that mammography did not detect tumors with a high proportion of proliferating cells (>20%) than tumors with a low proportion of proliferating cells (<5%) (odds ratio OR = 4.09; 95% confidence interval CI = 1.14-14.65). The OR for mammographic failure was 2.96 (95% CI = 1.07-8.20) among cancers that expressed p53 compared with cancers that did not. Interval cancers also had fewer apoptotic cells. Approximately 75% of interval cancers appear to have tumors with 5% proliferating cells or more. Younger women had a higher proportion of rapidly proliferating and aggressive cancers. CONCLUSION: Rapidly growing and aggressive tumors account for a substantial proportion of mammographic failure to detect breast cancer, especially among younger women, who have a high proportion of aggressive cancers.